Clinical Trials /

Study of M3814 in Combination With Capecitabine and Radiotherapy in Rectal Cancer

NCT03770689

Description:

The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) of M3814 in combination with capecitabine and radiotherapy (RT) in Phase Ib and to evaluate the efficacy of M3814 in terms of Pathological Clinical Response (pCR)/Clinical Complete Response (cCR) when administered in combination with capecitabine and RT versus placebo, capecitabine, and RT in Phase II.

Related Conditions:
  • Rectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of M3814 in Combination With Capecitabine and Radiotherapy in Rectal Cancer
  • Official Title: A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor M3814 in Combination With Capecitabine and Radiotherapy in Participants With Locally Advanced Rectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: MS100036_0020
  • SECONDARY ID: 2018-002275-18
  • NCT ID: NCT03770689

Conditions

  • Locally Advanced Rectal Cancer

Interventions

DrugSynonymsArms
Phase Ib: M3814Peposertib, MSC2490484APhase Ib: M3814 + Capecitabine + RT
CapecitabinePhase II: M3814 + capecitabine + RT
Phase II: M3814Peposertib, MSC2490484APhase II: M3814 + capecitabine + RT
Phase II: PlaceboPhase II: Placebo + capecitabine + RT

Purpose

The main purpose of the study is to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) of M3814 in combination with capecitabine and radiotherapy (RT) in Phase Ib and to evaluate the efficacy of M3814 in terms of Pathological Clinical Response (pCR)/Clinical Complete Response (cCR) when administered in combination with capecitabine and RT versus placebo, capecitabine, and RT in Phase II.

Trial Arms

NameTypeDescriptionInterventions
Phase Ib: M3814 + Capecitabine + RTExperimental
  • Phase Ib: M3814
  • Capecitabine
Phase II: M3814 + capecitabine + RTExperimental
  • Capecitabine
  • Phase II: M3814
Phase II: Placebo + capecitabine + RTPlacebo Comparator
  • Capecitabine
  • Phase II: Placebo

Eligibility Criteria

        Inclusion Criteria:

          -  Participants who have an Eastern Cooperative Oncology Group Performance Status less
             than or equals to (≤) 1

          -  Participants who have histologically confirmed and localized resectable rectal cancer
             (Stage III).

          -  Participants who received induction chemotherapy are allowed to be enrolled to this
             study except this induction is resulting in complete response.

          -  Participants who have lower edge of the tumor located in rectum

          -  Adequate hematological, hepatic and renal function as defined in the protocol

          -  Male participants if they agree to the following during the study intervention period
             and for at least 12 weeks after the last dose of study intervention

          -  Female participants are eligible if not pregnant or breastfeeding

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Participants with history of any other significant medical disease or psychiatric
             conditions that might in the assessment of the Investigator preclude safe
             participation in the study

          -  Participants with history of difficulty swallowing, malabsorption, or other chronic
             gastrointestinal disease or conditions that may hamper compliance and/or absorption of
             the study intervention

          -  Unstable cardiovascular function within 6 months prior to enrollment

          -  Hypertension uncontrolled by medication (ie, systolic blood pressure >= 150 millimeter
             of mercury (mmHg) and diastolic blood pressure >= 90 mmHg)

          -  Participants with history of other malignant disease within the past 5 years, other
             than successfully treated basal carcinoma of the skin or carcinoma in situ of the
             cervix

          -  Participants with known human immunodeficiency virus positivity, known active
             hepatitis (for example, hepatitis B virus or hepatitis C virus), current alcohol
             abuse, or cirrhosis

          -  Participants with ongoing active infection other than human immunodeficiency virus,
             hepatitis B virus, or hepatitis C virus, or treatment with a live attenuated vaccine
             within 4 weeks of dosing

          -  Participants with concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or
             unable to stop at least 5 days prior to the first treatment). Note that calcium
             carbonate is acceptable

          -  Participation in any interventional clinical study within 28 days prior to Screening
             or during participation in this study

          -  Other protocol defined exclusion criteria could apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase Ib: Number of Participants Experiencing a Dose Limiting Toxicity (DLT)
Time Frame:Time from first dose of study drug to end of chemo radiotherapy with a final assessment at 4 weeks post-surgery
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase Ib and II: Occurrence of Treatment-related Adverse Events (TEAEs) According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5.0
Time Frame:Time from first dose of study drug to final assessment at 5 years for each phase
Safety Issue:
Description:
Measure:Phase Ib and II: Number of Participants With Abnormalities (Grade Greater than or equals to (≥) 3) in Laboratory Test Values
Time Frame:Time from first study drug to final assessment at 5 years for each phase
Safety Issue:
Description:
Measure:Phase Ib and II: Number of Participants With Markedly Abnormal Vital Sign Measurements
Time Frame:Time from first dose of study drug to final assessment at 5 years for each phase
Safety Issue:
Description:
Measure:Phase Ib and II: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
Time Frame:Time from first dose of study drug to final assessment at 5 years for each phase
Safety Issue:
Description:
Measure:Phase Ib: Overall Survival
Time Frame:Time from first dose of study drug to final assessment at 5 years
Safety Issue:
Description:
Measure:Phase Ib: Disease-free Survival
Time Frame:Time from first study drug to final assessment at 5 years
Safety Issue:
Description:
Measure:Phase Ib: Best Overall Response Assessed by Investigator
Time Frame:Time from first dose of study drug until surgery at Day 119
Safety Issue:
Description:
Measure:Phase Ib and II: Time from Surgery to Local Recurrence and Distant Metastasis
Time Frame:Time from surgery to final assessment at 5 years for each phase
Safety Issue:
Description:
Measure:Phase Ib: Maximum Observed Drug Concentration (Cmax) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day (FD1) and Fraction Day 9
Safety Issue:
Description:
Measure:Phase Ib: Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (tlast) (AUC0-t) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9
Safety Issue:
Description:
Measure:Phase Ib: Time to Reach Maximum Plasma Concentration (tmax) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9
Safety Issue:
Description:
Measure:Phase Ib and II: Total Body Clearance of Drug From Plasma Following Oral Administration (CL/f) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 for each phase for each phase
Safety Issue:
Description:
Measure:Phase Ib and II: Apparent Volume of Distribution (Vz/f) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9 for each phase
Safety Issue:
Description:
Measure:Phase Ib: Apparent Terminal Half-life (t1/2) of M3814
Time Frame:Pre-dose, 1, 2, 3 and 4 hour post-dose on Fraction Day 1 and Fraction Day 9
Safety Issue:
Description:
Measure:Phase II: Overall Survival
Time Frame:Time from randomization to final assessment at 5 years
Safety Issue:
Description:
Measure:Phase II: Best Overall Response Assessed by Investigator
Time Frame:Time from randomization until Day 119
Safety Issue:
Description:
Measure:Phase II: Neoadjuvant Rectal Score
Time Frame:Post-surgery at Day 119
Safety Issue:
Description:
Measure:Phase II: Proportion of Participants With/Without Surgical Intervention
Time Frame:Time from randomization to final assessment at 5 years
Safety Issue:
Description:
Measure:Phase II: Number of Participants With R0 Resection (No Residual Tumor)
Time Frame:Post-surgery at Day 119
Safety Issue:
Description:
Measure:Phase II: Quality of Life (QoL) Measured Using European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30)
Time Frame:Time from randomization to assessment at 2 years
Safety Issue:
Description:
Measure:Phase II: Quality of Life (QoL) Measured Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Colorectal Cancer (EORTC-CR29)
Time Frame:Time from randomization to assessment at 2 years
Safety Issue:
Description:
Measure:Phase II: Quality of Life (QoL) Measured Using EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)
Time Frame:Time from randomization to assessment at 2 years
Safety Issue:
Description:
Measure:Phase Ib and II: Proportion of Participants With Pathological Complete Response (pCR)
Time Frame:Post-surgery at Day 119
Safety Issue:
Description:
Measure:Phase Ib: Proportion of Participants With Clinical Complete Response (cCR)
Time Frame:Time from first study drug until 1 to 2 weeks prior to surgery
Safety Issue:
Description:
Measure:Phase II: Proportion of Participants With Clinical Complete Response (cCR)
Time Frame:Time from randomization until surgery at Day 119
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • DNA-PK inhibitor
  • M3814
  • capecitabine

Last Updated

October 16, 2020